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Generation of advanced cerebellar organoids for neurogenesis and neuronal network development

ABSTRACT: Generation of advanced cerebellar organoids for neurogenesis and neuronal network development

PROVIDER: PRJNA996942 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25374577_1.fastq.gz	Fastqsanger.gz
	SRR25374577_2.fastq.gz	Fastqsanger.gz
	SRR25374578_1.fastq.gz	Fastqsanger.gz
	SRR25374578_2.fastq.gz	Fastqsanger.gz
	SRR25374579_1.fastq.gz	Fastqsanger.gz

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Generation of advanced cerebellar organoids for neurogenesis and neuronal network development

Project description:Neurons within the cerebellum form temporal-spatial connections through the cerebellum, and the entire brain. Organoid models provide an opportunity to model the early differentiation of the developing human cerebellum, which is difficult to study in vivo, and affords the opportunity to study neurodegenerative and neurodevelopmental diseases of the cerebellum. Previous cerebellar organoid models focused on early neuron generation and single cell activity. Here, we modify previous protocols to generate more mature cerebellar organoids that allow for the establishment of several classes of mature neurons during cerebellar differentiation and development, including the establishment of neural networks during whole organoid maturation. This will provide a means to study the generation of several more mature cerebellar cell types, including Purkinje cells, granule cells, interneurons expression as well as neuronal communication for biomedical, clinical, and pharmaceutical application.

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Project description:Human induced pluripotent stem cells (iPSCs) have great potential for disease modeling. However, generating iPSC-derived models to study brain diseases remains a challenge. In particular, the ability to recapitulate cerebellar development in vitro is still limited. We presented for the first time a reproducible and scalable production of cerebellar organoids by using the novel Vertical-Wheel single-use bioreactors, in which functional cerebellar neurons were obtained. Here, we evaluate the global gene expression profiles by RNA sequencing (RNA-seq) across cerebellar differentiation, demonstrating a faster cerebellar commitment in this novel dynamic differentiation protocol. Furthermore, transcriptomic profiles suggest a significant enrichment of extracellular matrix (ECM) in dynamic-derived cerebellar organoids, which can better mimic the neural microenvironment and support a consistent neuronal network. The presence of factors that favors angiogenesis onset was detected in dynamic condition, which can enhance functional maturation of cerebellar organoids. We anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

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Atr maintains chromosomal integrity during postnatal cerebellar neurogenesis

Project description:Atr maintains chromosomal integrity during postnatal cerebellar neurogenesis

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Atr maintains chromosomal integrity during postnatal cerebellar neurogenesis [Affymetrix]

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Atr maintains chromosomal integrity during postnatal cerebellar neurogenesis [RNA-Seq]

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Human Cerebellar Organoids with functional Purkinje Cells

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